Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction.

Ivabradine inhibits hyperpolarization-activated cyclic nucleotide-gated channels in the sinus node, thereby reducing heart rate, and heart rate reduction improves regional myocardial blood flow and contractile function in ischemic myocardium. Accordingly, ivabradine reduces anginal symptoms in patients with stable coronary artery disease but does not improve their clinical outcome. Heart rate reduction with ivabradine in patients with symptomatic heart failure reduces symptoms, attenuates remodeling, and improves clinical outcome. In pigs and mice, ivabradine reduces infarct size from myocardial ischemia/reperfusion, even when heart rate reduction is abrogated by atrial pacing. Improved viability is also observed in isolated ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. These beneficial effects are attributed to reduced reactive oxygen species formation from the mitochondria. There is also evidence for a heart rate-independent benefit from ivabradine in the vasculature of mice and humans, and in left ventricular contractile function of pigs. Finally, in mice, ivabradine also has anti-aging potential.